Our goal is to study the carcinogenic effects of ionizing radiation in utero on the developing fetus. Investigations will concentrate on two posited phases in the preleukemic stage by assessment of any immunochemical and biochemical alteration of the in utero irradiated thymocytes and splenic cells, and any immunobiologic modifications of the fetal cells or the feto-maternal relationship. Surface phenotype changes (immunochemistry) will be quantitatively and qualitatively assayed by radioimmunoassay, quantitative absorption cytotoxicity tests, and one- and two- dimensional electrophoretic gel analysis. Analysis of biochemical alterations will focus on differences in protein and nonprotein cellular thiols. Immunobiologic evaluation of postnatal thymocytes and lymphocytes which were irradiated in utero will be quantitated in in vitro cellular proliferative assays in the absence or presence of secondary stimulatory factors such as mitogen, IL1 and IL2 (immunoregulatory factors), and/or a tumor promoter (TPA). Immunoreactivity between maternal and fetal cells also will be examined in vitro. Radiation is known to produce leukemogenesis and the expression of Qa2 and TL antigens on previously Qa2- and TL- C57B1/6 lymphocytes, but the ability of radiation in utero to alter the chemistry and biology of fetal cells has not been studied adequately. In addition to the possible induction of neoantigens, radiation may modulate existing antigens such as H-2K/D and Ia. All of these antigens of the 17th chromosome of mice have important roles in immune functioning and a change in surface phenotype could affect leukemogenesis directly or via maternal responses. If preleukemic changes are detectable, in vitro and in vivo development of malignant cells will be monitored.